USCA 2015 Introductions Russell Campbell, Office of HIV/AIDS Network - PowerPoint PPT Presentation

USCA 2015

Introductions Russell Campbell, Office of HIV/AIDS Network Coordination Cynthia Lee, Tuberculosis Trials Consortium Community Research Advisors Group Rona Siskind, Division of AIDS

Presenters Cynthia Lee Rona Siskind Russell Campbell

Overview • TB-HIV – Russell Campbell • Integration of TB and HIV in Research and Practice – Cynthia Lee • TB-HIV International Community Partnership – Rona Siskind • Q & A

Acknowledgements • TBTC CRAG • Community Partners • Mike Frick • Jeff Schouten

TB-HIV Assessment ID USCA 2015 TB/HIV Workshop Assessment Please indicate whether you believe the following statements to be true or false about TB/HIV . If you are unsure, feel free to select “don’t know.” Don’t True False know Globally, TB is the leading cause of death in people with HIV. 1. T F DK 12 million persons are TB/HIV co-infected. 2. T F DK 3. All TB drugs can be taken along with HIV medications. T F DK People living with HIV are less likely to have TB outside of the 4. T F DK lungs. TB is easier to diagnose in people living with HIV; their sputum 5. T F DK samples may often show infection. People with HIV and latent TB infection are urged to take medicine 6. T F DK to prevent progression to active TB disease. 7. In the United States, more money is spent on TB research than on T F DK HIV research . Once someone has been treated for TB, they can never be re- 8. T F DK infected. Starting ART therapy early does not prevent progression to active 9. T F DK TB disease in people with HIV and latent TB infection. TB accounts for approximately one in four HIV-related deaths. 10. T F DK

USCA 2015 Integration of TB and HIV in Research and Practice Community Partners & Community Research Advisors Group September 11, 2015 Cynthia C Lee, EdD, MS, MA, CHES CRAG Member

About the CRAG • an international, community-based advisory body • ensures the meaningful engagement of TB-affected communities in research conducted by the TBTC • supports a TBTC research agenda that is responsive to community needs and scientific priorities 8 members from TBTC sites in 6 countries: • United States • South Africa • Uganda • Vietnam • Spain • Peru

TBTC Sites

About the TBTC Tuberculosis Trials Consortium • Research network at US Centers for Disease Control Department of TB Elimination • Conducts drug research for TB infection and TB disease • Mission to conduct programmatically-relevant research 8 U.S. sites (Texas, New York, Tennessee, California, Washington, D.C.) 8 International sites (Spain, Peru, South Africa, Vietnam, Uganda, Kenya, Hong Kong)

Priorities issues in TB research • Long duration (6 months for DS-TB; 2 years for MDR-TB; • High pill burden (up to 12 pills/day for DS-TB; up 15,000 pills for full course of MDR-TB treatment) • Toxic side-effects (irreversible deafness; neuropathy; skin discoloration; psychosis; vomiting) • Painful injectables (for early stage of MDR-TB treatment)

Why integrate TB and HIV in research and practice? 2013 WHO Report: • 9 million people developed TB, 1.5 million TB deaths • 1.1 million PLHIV developed TB (4/5 of these in Africa) • 360,000 people with HIV died of TB • 510,000 women died from TB; 1/3 of these were women with HIV • 70% of PLHIV with TB are on ARVs • 40% of TB patients know their HIV status

TB/HIV: One disease… “The reality is that in sub -Saharan Africa, TB and HIV are one disease. We must treat them together.” –– Mark Dybul, Global Fund “We need to integrate TB and HIV and treat these as one disease.” –– Jarbas Barbosa, Brazil “Life is forcing us to put TB and HIV together.” –– Aaron Moatsaledi, South Africa

… with two research agendas? 1. Money spent on research: HIV: US 2.6 billion, (drug R&D, 2011) TB: US 676.6 million, (all R&D, 2013) 2. Number of new drugs approved by FDA since 1987: HIV: 36 drugs TB: 2* drugs 3. Number of clinical trials behind the newest drugs: HIV: Dolutegravir, 61 trials TB: Delamanid, 6 trials

Key Populations — some shared, some different Global Fund definition of “key population” Epidemiologically, group faces increased risk 1. Access to relevant services is lower for the group 2. The group faces frequent human rights violations or marginalization 3. TB Key Populations • Prisoners “All people living with HIV, • People with HIV • Migrants and refugees and who currently have, or • Miners have survived, TB, fall within • Healthcare workers • People who use drugs and this definition of key alcohol populations” • Children and adolescents Are these key populations equitably represented in TB and TB/HIV R&D?

Where are people with HIV in TB R&D? • PLHIV often in phase IIb and III studies, but at higher CD4 counts (≥250) • PLHIV on ARVs less frequently included in phase IIb and III trials • People with extra-pulmonary TB, including many PLHIV, are almost always excluded from trials • Children with HIV often not included in trials

What needs to change? • Having HIV shouldn’t be an exclusion criteria for TB drug research • Taking ARVs shouldn’t be an exclusion criteria, either • DDI studies between TB and HIV drugs need to happen sooner — preferably by time TB drug enters phase IIa trials • TB investigators need to become more comfortable enrolling PLHIV • HIV investigators need to become better acquainted with TB research

CAN TB AND HIV DRUGS BE USED TOGETHER? It’s complicated.

Activist Guide to Clinical Trials Protocols A Protocol Review Companion for Activists Written by Cynthia C Lee Edited by Lindsay McKenna, Mike Frick, and the CRAG January 2015 19

Example: MDR-TB drug bedaquiline Not yet studied in people with TB/HIV who are using ARVs. Not been studied in people who use drugs or may be on opioid substitution therapies. Small studies giving people HIV medicines and a single dose of bedaquiline at a time suggest: • Efavirenz : appears to reduce amount of bedaquiline in the body by about half • Lopinavir/ritonavir : slightly raises the amount of bedaquiline in the body • Ketoconazole : increases the amount of bedaquiline in the body; patients taking ketoconazole and bedaquiline have an increased risk of QT prolongation

Where are children in TB R&D? The “missing cohort” of TB research Adolescent Trial Phase TB Type Regimen Inclusion ✖ C213 III MDR DLM + OBR (18 – 24 months) Stage 1: 9 month w/ injectable ✖ STREAM III MDR Stage 2: 9 month all oral w/ BDQ 6 month w/ injectable + BDQ ? STAND III DS/MDR 6 month all oral (PaMZ) ✔ Nix-TB IIb XDR 6 – 9 month all oral (Pa,LZD,BDQ,Z?) (14+ yrs.) ? MARVEL IIb MDR Shortened regimen (novel drugs – TBD) ✖ NC005 IIb DS/MDR Shortened regimen (BDQ,Pa,Z) ✔ 4 month HPZE/HP TBTC S31 III DS 4 month HPZM/HPM (12+ yrs.)

Where do we go from here? • Greater collaboration between TB and HIV research networks • Progressive inclusion of people with HIV (including those taking ARVs) in TB clinical trials • Earlier inclusion of adolescents and children (including those with HIV) in TB clinical trials • Earlier and more comprehensive drug-drug interaction studies: between TB/TB drugs; and TB/HIV drugs • More research designed to address key challenges facing TB/HIV treatment and prevention (pill burden; drug-drug interactions; long treatment duration; patient- friendly delivery systems; extra-pulmonary TB) • Increased joint TB/HIV research activities and funding commitments for these activities

THANK YOU mike.frick@treatmentactiongroup.org http://crag-tb.tumblr.com/

USCA 2015 TB-HIV International Community Partnership Community Partners & Community Research Advisors Group September 11, 2015 Rona Siskind, MHS Division of AIDS National Institute of Allergy & Infectious Diseases National Institutes of Health

NIAID/DAIDS Strategic Goals • NIAID : Provide the scientific basis for achieving an “AIDS - free generation” by developing a safe and effective HIV vaccine as well as improved combination prevention strategies, optimization of treatment modalities, and novel therapeutic approaches towards a cure for HIV infection • DAIDS : Develop and support the infrastructure and biomedical research needed to : 1. Halt the spread of HIV through the development of an effective vaccine and biomedical prevention strategies that are safe and desirable 2. Develop novel approaches for the treatment and cure of HIV infection 3. Treat and/or prevent co-infections and co-morbidities of greatest significance 4. Foster partnerships with scientific and community stakeholders to develop and implement effective interventions

NIH HIV/AIDS Clinical Trials Networks

NIH Networks & Community Engagement National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) Clinical Trials Networks ACTG Global CAB MTN HPTN CWG CWG Community Partners HVTN IMPAACT Global ICAB CAB Site CAB

Network Clinical Research Sites Community Partners organized through the HIV/AIDS Network Coordination Office